A significant morbidity and mortality is associated with chronic uremia due to end stage renal disease in humans. A number of endocrine and metabolic disturbances have been described in chronically uremic patients. The principle objective of this proposal has been to study the effects of altered endocrine regulations upon carbohydrate metabolism in patients with end stage renal disease. The studies will employ safe stable isotopic tracers and mass-spectrometric techniques. Quantative measurements of fluxes of major metabolic substrates for oxidative metabolism will be done in uremic subjects and key-regulatory steps will be examined in animal model. Thus, these studies will evaluate the relationship between major body fuels. Quantification of these data will be helpful in better understanding of metabolic perturbations in chronic uremia and will aid in the development and testing of new therapeutic regimens.